Background: Systemic sclerosis (SSc) is an autoimmune disease with interstitial lung disease (ILD) representing the leading cause of mortality. Diaphragmatic muscle impairment, which may contribute to respiratory dysfunction, is underexplored in SSc. Objective: This study aimed to assess diaphragmatic thickness using HRCT in patients with SSc-ILD and to investigate whether this parameter correlates with disease severity and clinical outcomes. Methods: We conducted a multicentric retrospective observational study that included 161 participants: 69 with SSc-ILD and 92 matched controls without pulmonary disease. Preliminary findings from this cohort were previously communicated as a conference abstract at EULAR 2024. Diaphragmatic thickness was measured on axial and coronal CT images at the celiac axis level by two independent radiologists. Clinical and functional parameters were collected, including forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), echocardiographic findings, and 6 min walking test performance. Results: The left hemidiaphragm was significantly thinner in patients with SSc-ILD compared with controls (2.98 ± 1.04 mm vs. 3.44 ± 0.97 mm; p = 0.004), while the right hemidiaphragm showed a non-significant trend toward reduction (3.21 ± 1.09 mm vs. 3.52 ± 1.05 mm; p = 0.072). Thinning of the right hemidiaphragm correlated significantly with lower FVC (p < 0.05). ROC analysis identified an optimal left diaphragm cut-off of ≤3.115 mm (AUC = 0.635, 95% CI: 0.556-0.709, sensitivity = 66.7%, specificity = 60.9%). No associations were found with the autoantibody profile, disease duration, or treatment. Interobserver reliability was excellent (Bland-Altman mean difference -0.002 mm, p = 0.95). Conclusions: HRCT-measured left hemidiaphragm thickness is significantly reduced in patients with SSc-ILD compared with controls, and right hemidiaphragm thickness correlates with impaired lung function. Although its discriminative performance is modest (AUC 0.635), this parameter may serve as a supplementary zero-burden addition to routine HRCT evaluation alongside pulmonary function tests. The retrospective cross-sectional design precludes conclusions about causality or prognosis; prospective studies incorporating concurrent functional diaphragm assessment are warranted.

Systemic sclerosis (SSc) is a rare, complex, chronic, progressive, severe, often life-threatening, fibrosing, heterogeneous autoimmune connective tissue disease with immune dysfunction and limited treatment options. Interstitial lung disease (ILD) is common in SSc. To study the clinical characteristics of systemic sclerosis-associated interstitial lung disease (SSc-ILD) will provide evidence for the early diagnosis, treatment decision-making, and prognosis of SSc-ILD patients. One hundred and seventy-five patients with SSc were retrospectively enrolled and divided into SSc-ILD group and SSc-non-ILD group. The general clinical characteristics, autoantibodies, laboratory test, thorax high-resolution computed tomography (HRCT), pulmonary function testing, stratification, and treatment options were compared between the 2 groups. The risk factors of SSc-ILD were also analyzed. One hundred and twenty-four SSc-ILD patients (70.9%) and 51 SSc-non-ILD patients (29.1%) were in 175 SSc patients. Raynaud phenomenon, skin swelling, and joint involvement were the top 3 initial symptoms. Sixty-seven SSc-ILD patients (54.1%) showed new onset or progression of ILD on HRCT, which were heterogeneous. The significantly increased indicators in SSc-ILD group were gastrointestinal involvement (P = .003), antinuclear antibody (ANA) (P = .006), anti-Scl-70 (P <.001), anti-SSA (P = .008), and rheumatoid factor (P = .04), erythrocyte sedimentation rate (ESR) (P = .005), CRP (P = .000), IL-6 (P = .001), globulin (P = .006), IgG (P = .002), IgA (P = .001), while the decreased indicators were mean corpusular hemoglobin concerntration (P = .036), albumin (P = .046), liver dysfunction (P = .018), and FVC% (P = .006). Positive anti-Scl-70 antibody and decreased FVC% were independent risk factors for SSc-ILD. The incidence of ILD occurrence and progression was significantly higher in patients with anti-Scl-70 antibody, diffuse cutaneous systemic sclerosis (dcSSc) plus anti-Scl-70 antibody, ESR ≥50 mm/h, and CRP ≥5.00 mg/L (P <.05). Based on the predictive factors (gastrointestinal involvement, joint involvement, positive anti-Scl-70 antibody, liver dysfunction, duration of disease, FVC%, mean corpusular hemoglobin concerntration, ESR, CRP, IgG, IgA, globulin, and albumin), independent risk factors (anti-Scl-70 antibody and decreased FVC%), clinical phenotypic and autoantibody stratification, HRCT heterogeneity, and atypical initial symptoms, it may be seized the "window of opportunity" with early diagnosis may exist for preventing the irreversible progression of pulmonary fibrosis of SSc-ILD patients.

INTRODUCTION: Antimitochondrial antibodies (AMA), the hallmark of primary biliary cholangitis (PBC), have been inconsistently reported and poorly characterized in systemic sclerosis (SSc). Although recently linked to subclinical dysmotility in a cohort enriched for gastrointestinal (GI) involvement, data on the prevalence and clinical relevance of AMA in real-life SSc cohorts remain limited. METHODS: A retrospective cross-sectional study was conducted on consecutive SSc patients followed at a referral center for the disease. Patients were tested for serum AMA according to reference standards, including HEp-2 immunofluorescent screening and ELISA confirmation (anti-E2 pyruvate dehydrogenase). Patients’ features were compared between AMA-positive and -negative cases. RESULTS: Among 165 SSc patients (20% diffuse cutaneous disease, 33% interstitial lung disease, 7.3% pulmonary arterial hypertension; 51% positive for anticentromere antibodies, 29% anti-topoisomerase I, 12% anti-RNA polymerase III), 37 (22%) were AMA-positive. While strongly associated with PBC, AMA were not linked to significant differences in cutaneous, vascular, pulmonary, or myocardial involvement. However, AMA were associated with GI vascular involvement (OR 13.3, 95% CI 2.53–95.0; p = 0.002), including gastric antral vascular ectasia (OR 7.99, 95% CI 1.05–72.5; p = 0.045), independently from PBC or symptoms of SSc-GI involvement. These complications are clinically relevant, as they may lead to GI bleeding and refractory iron-deficiency anemia. CONCLUSION: In our cohort of SSc patients systematically screened for autoantibodies, we found a high prevalence of AMA and identified a novel putative association with GI vascular involvement, which warrants confirmation in independent studies.

Juvenile systemic sclerosis (jSSc) is a rare multisystem autoimmune disease, representing 4-10 % of systemic sclerosis (SSc) cases, and causes significant morbidity during growth and development. While sharing features with adult-onset disease, jSSc differs in phenotype, with more frequent diffuse cutaneous involvement, overlap syndromes, distinct autoantibody profiles and different outcomes. Evidence to guide care remains limited because of disease rarity and the lack of paediatric trials. This review summarises epidemiology, classification, clinical features and outcomes of jSSc, highlighting differences from adult disease. A structured approach to assessment is presented, emphasizing regular multisystem evaluation. Organ-specific assessment of skin, lung, cardiac, gastrointestinal, musculoskeletal, renal and vascular involvement, alongside patient- and parent-reported outcomes, is discussed. Management strategies are reviewed using paediatric consensus recommendations and extrapolated adult data, emphasizing specialist paediatric rheumatology care within multidisciplinary teams. Emerging therapies, including autologous haematopoietic stem cell transplantation, and issues of psychosocial impact and transition to adult care are addressed.

BACKGROUND: Although systemic sclerosis (SSc) predominantly affects the female sex, male patients tend to present a more severe visceral profile and worse prognosis. This study aims to analyze the clinical and laboratory characteristics of male patients in a large single SSc cohort. METHODS: This retrospective study analyzed 700 patients followed regularly at a single tertiary outpatient SSc center. Patients were classified according to the 2013 ACR/EULAR SSc criteria, and all data were retrieved from an electronic database. Statistical analyses included comparing demographic and clinical data, Kaplan-Meier survival curves, and multivariate analyses using SigmaStat 14.5. RESULTS: There were 612 women (87.4%) and 88 men (12.6%). Male patients were more frequently African-Brazilians (p = 0.005), and showed a significantly shorter disease duration compared to females (10.1 vs. 13.8 years, p < 0.001), with higher rates of environmental exposures (37.5% vs. 8.2%, p < 0.001), and more severe fibrotic manifestations, including skin thickening score (p = 0.004), diffuse SSc (p = 0.005), and extensive interstitial lung disease (p = 0.013). Men also had higher rates of group 3 pulmonary hypertension (p = 0.018), congestive heart failure (p = 0.001), and required more aggressive treatments such as cyclophosphamide (p < 0.001) and rituximab (p = 0.002). Although there were no significant sex differences in the frequency of vascular manifestations or joint involvement, men had lower rates of positivity for antinuclear antibodies (ANA) (p = 0.047) and anti-centromere antibodies (ACA) (p = 0.001). Male sex was associated with increased mortality (hazard ratio 2.3; 95% CI 1.4 to 3.8; p = 0.002) and survival rates at 1, 3, 5, and 10 years from diagnosis were 99.2%, 96%, 89%, and 75% for men, and 99%, 98%, 97%, and 93% for women (p < 0.001). CONCLUSION: Our study reinforces the association between male sex and more severe SSc, marked by greater skin involvement, worse pulmonary and cardiac outcomes, a higher prevalence of environmental exposures, and lower ACA positivity. These factors contributed to poorer survival outcomes in men compared to women. These findings underscore the need for a more comprehensive evaluation of clinical manifestations to better assess disease progression in male SSc patients.